Background: Glycophorin A (GPA) is one of two glycoproteins found on the surface of human red blood cells (RBCs) that constitute the MNS blood group system. The structure of GPA's extracellular domain is unknown despite previous attempts using X-ray crystallography and NMR spectroscopy. As a result, there is a knowledge gap regarding antigen presentation. This hinders the production of monoclonal antibodies (mAbs) against MNS antigens. Methods: In silico modelling techniques including homology modelling and ab initio predictions were implemented to develop a proposed structure for the monomeric form of the GPA extracellular domain. Developed structures were then subjected to molecular dynamics (MD) simulations. Results: The results obtained indicated that the monomeric extracellular domain of GPA is most likely intrinsically disordered, with the exception of a β-hairpin-like structure spanning the exon 3-4 junction. Further analysis showed this β-hairpin-like structure was not observed when starting from an extended or cyclical peptide structure within the time-scale used in the MD simulation study, suggesting that linear or cyclical peptide fragments of this region are unsuitable representations for the purposes of antigen presentation. Lastly, of the MNS antigens produced by single amino acid variations found in the exon 3-4 junction, only the ERIK antigen (p.Gly78Arg; MNS37) was found to alter the β-hairpin-like structure. Conclusions: The monomer of the extracellular domain of GPA has a high level of disorder, with the exception of the antigenic exon 3-4 junction, which adopts a β-hairpin-like structure. Our work suggests that linear peptides and expression of the monomeric form of GPA might be of limited use for immunisation or screening processes used in antibody identification. Further understanding of the antigenic determinants of GPA will require a more sophisticated combination of laboratory and computational approaches, as well as consideration of possible structural changes as a result of dimerisation.